Process for the preparation of derivatives of beta-(p-hydroxyphenyl)-isopropylamine



Patented Feb. 7, 1939 PATENT OFFICE PRO CE S 8 FOR RIVATIVESISOPROPYLAMINE Gustav Hildebrandt, Mannheim,

OF B- (D- THE PREPARATION OF DE.-

YDROXYPHENYL) Germany, as-

signor to E. Bilhuber Inc., Jersey City, N. J

No Drawing.

Application December 23, 1937, Se-

rial No. 181,459. In Germany December 31,

1 Claim.

This invention relates to the preparation of derivatives of[i-(p-hydroxyphenyl) -isopropylamine of the general formulaHO-CsH4-CHz-CE-CHz YN-X In this formula X designates hydrogen, an alkylradical, for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl,isoamyl, etc., or a cyclo- 10 alkyl radical, for example cyclohexyl morp-methyl-cyclohexyl, tetrahydronaphthyl, decahydronaphthyl, etc., and Yan alkyl radical containing at least two carbon atoms, for exampleethyl, propyl, isopropyl, butyl, isobutyl, isoamyl, 15 etc., or acycloalkyl radical such as cyclohexyl.

It has already been proposed to prepare {3-(pmethoxyphenyl)-isoproplmethylamine by cond e n s in g c-(p-methoxyphenyl) -isopropylamine with benzaldehyde to form thecorresponding Schifis base, treating the Schifis base with methyl iodideor a similar compound and hydrolysing the resulting addition productwith aqueous acid. The resulting ,B-(p-methoxyphenyl)-isopropylmethylamine may be converted by demethylation intop-(p-hydroxyphenyl) -isopropylmethylamine, which according to knowndata. is physiologically active and is said to exert actions similar tothose of ephedrine. According to the process of U. S. A. patentapplication Serial No. 144,545 the p-(p-hydroxyphenyD-isopropylamine istreated with methylating agents.

According to this invention it has been found that the favourabletherapeutic properties of ,3- (p-hydroxyphenyl) -isopropylmethylamine ar e not limited to these substances alone but that substances of thelike favourable therapeutic properties are obtained ifB-(p-hydroxyphenyD- isopropylamine is treated with alkylating orcycloalkylating agents. In this way products are obtained of the generalformula HOCsH4CHr-CH-GH3 Y-N-x in which X is hydrogen, an alkyl radicalor a cycloalkyl radical and Y is an alkyl radical containing at leasttwo carbon atoms or a cycloalkyl radical. In the production of theseproducts the alkylating or cycloalkylating agents are so selected thatthey yield either X or Y or X and Y.

The process of this invention may be carried into effect by treating theB-(p-hydroxyphenyl) lected from the group consisting isopropylamine withknown alkylating or cycloalkylating agents. 'I'husfor example theinitial base may be heated with diethyl sulphate. An other knownalkylating method consists in heating the initial base with alkylhalides, for example butyl, isobutyl or isoamyl halides, for examplebromides or iodides. Finally the alkylation may be effected bycondensing the base with aldehydes or ketones and simultaneouslyeffecting reduction, for example by condensingp-(phydroxyphenyl)-isopropylamine with acetone and simultaneouslyreducing, whereby B- (p-hydroxyphenyl)-isopropyl-isopropylamine isobtained.

In like manner in order to prepare cycloalkyl derivatives 5-(p-hydroxyphenyl) -isopropylamine may be treated withknowncycloalkylating agents, for example by condensing withcycloaldehydes or ketones and simultaneously reducing.

Ewample 15.1 gms. of p-(p-hydroxyphenyl)-isopropylain which X is a.radical selected from the group consisting of hydrogen, lower alkyl, andcycloalkylradicals and in which Y is a radical seof lower alkyl radicalshaving at least two carbon atoms and cycloalkyl radicals, which consistsin contacting p- (p-hydroxyphenyl) -isopropylamine with agents selectedfrom the group consisting of lower alkylating and cycloalkylatingagents.

GUSTAV HILDEBRAND'I.

